There is no known underlying genetic defect predisposing patients to develop primary intraocular lymphoma (PIOL). Discovery of genetic factors predisposing to the development of PIOL would be of benefit for early diagnosis, prognostic staging, and development of novel treatments for PIOL. Until recently, genetic approaches to investigate the etiology of cancer have relied upon methods utilizing linkage based on traditional Mendelian inheritance patterns. It is probable that many diseases are a consequence of multiple genetic factors, and are therefore less amenable to study using traditional methods of linkage analysis and positional cloning to isolate single genes. Single nucleotide polymorphisms (SNPs) are the most common sources of variation in the human genome. SNPs are single-base differences in the DNA sequence that can be observed among individuals in a population. A SNP is defined on the basis of a frequency of at least 1% prevalence in one or more populations. SNPs are present throughout the genome at an average frequency of 1/1000 base pairs. We propose to analyze the frequency of SNPs specifically within the coding frames of biologically plausible genes responsible for function of the innate immune system. The interleukins are a specific pathway of interest because previous research has demonstrated derangements in the ratios of interleukins 10 and 6 in the vitreous humor and spinal fluid of patients with PIOL, leading to the hypothesis that altered function or expression of these or other interleukins could permit the development of this rare malignancy. Samples continue to be collected, but as no results have yet been obtained. We hosted a workshop on this subject at the NIH recently and we plan to contact participants to gain specimens for this rare tumor.